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Ferritinophagy is associated with tumor occurrence, development, and therapy effects. Ferritinophagy and ferroptosis are regulated by iron metabolism and are closely connected. LC3 protein is a key protein in autophagy. Following the binding of NCOA4 to FTH1, it links to LC3Ⅱ in lysosomes, a symbol of ferritinophagy. A ferritinophagy’s inducer is likely to open new avenues for anticancer medication research and development. In this study, we discovered that caryophyllene oxide has a substantial inhibitory effect on HCCLM3 and HUH7 cells, by regulating the level of cellular oxidative stress, and the levels of autophagy and iron metabolism in HCCLM3 and HUH7 cells, leading to a ferritinophagy-related phenomenon. Furthermore, the results of T-AOC, DPPH free radical scavenging rate, and hydroxyl radical inhibition indicated that caryophyllene oxide can inhibit cell anti-oxidation. The examination of the ferritinophagy-related process revealed that caryophyllene oxide promotes the production and accumulation of intracellular reactive oxygen species and lipid peroxidation. NCOA4, FTH1, and LC3Ⅱ were found to be targeted regulators of caryophyllene oxide. Caryophyllene oxide regulated NCOA4, LC3 Ⅱ, and FTH1 to promote ferritinophagy. In vivo, we discovered that caryophyllene oxide can lower tumor volume, significantly improve NCOA4 and LC3 protein levels in tumor tissue, and raise Fe2+ and malondialdehyde levels in serum. The compound can also reduce NRF2, GPX4, HO-1, and FTH1 expression levels. The reduction in the expression levels of NRF2, GPX4, HO-1, and FTH1 by caryophyllene oxide also inhibited GSH and hydroxyl radical’s inhibitory capacities in serum, and promoted iron deposition in tumor tissue resulting in the inhibition of tumor growth. In summary, our study revealed that caryophyllene oxide mostly kills liver cancer cells through ferritinophagy-mediated ferroptosis mechanisms. In conclusion, caryophyllene oxide may be used as a ferritinophagy activator in the field of antitumor drug research and development.

Knowledge graph embedding~(KGE) aims to represent entities and relations into low-dimensional vectors for many real-world applications. The representations of entities and relations are learned via contrasting the positive and negative triplets. Thus, high-quality negative samples are extremely important in KGE. However, the present KGE models either rely on simple negative sampling methods, which makes it difficult to obtain informative negative triplets; or employ complex adversarial methods, which requires more training data and strategies. In addition, these methods can only construct negative triplets using the existing entities, which limits the potential to explore harder negative triplets. To address these issues, we adopt mixing operation in generating harder negative samples for knowledge graphs and introduce an inexpensive but effective method called MixKG. Technically, MixKG first proposes two kinds of criteria to filter hard negative triplets among the sampled negatives: based on scoring function and based on correct entity similarity. Then, MixKG synthesizes harder negative samples via the convex combinations of the paired selected hard negatives. Experiments on two public datasets and four classical KGE methods show MixKG is superior to previous negative sampling algorithms.

Purpose Signal transducer and activator of transcription 3 (STAT3) is a DNA-binding protein that regulates various biologic processes, including cell growth, apoptosis, and malignant transformation. Abnormal activation of STAT3 is associated with many diseases, and there is currently no relevant study on the pathogenesis of pterygium. The purpose of this study was to investigate the expression and clinical significance of STAT3, HIF-1α, and VEGF in pterygium at different stages. Methods Immunohistochemistry was used to study the expression levels of STAT3, HIF-1α, and VEGF in 50 cases of pterygium and 20 cases of control conjunctival tissue. The expression intensity of the three proteins was evaluated with Image-Pro Plus 6.0 image analysis software. Results In the pterygium group, the positive rates for STAT3, HIF-1α, and VEGF were 82.0%, 86.0%, and 84.0%, respectively, while those in the normal conjunctiva group were 40.0%, 25.0%, and 15.0%. The expression of STAT3, HIF-1α, and VEGF in pterygium was higher than that in control conjunctiva, and the expression in advanced pterygium was statistically significantly higher than that in stationary pterygium (p < 0.01). The expression levels of STAT3 and HIF-1α in pterygium were related to the length and depth of the corneal invasion of pterygium. The expression level of VEGF in pterygium was related to the length of pterygium, but not to the depth. In addition, there was a significant positive correlation between the expression of STAT3, HIF-1α, and VEGF (p < 0.01). Conclusions For the first time, the expression levels of the STAT3, HIF-1α, and VEGF proteins were detected simultaneously in pterygium tissue. Compared with normal conjunctiva, STAT3, HIF-1α, and VEGF were highly expressed in pterygium, and the expression in advanced pterygium tissue was more significant than in the stationary pterygium tissue. It is suggested that STAT3 may directly or through HIF-1α promote VEGF expression and participate in the growth and angiogenesis of pterygium. Targeting STAT3 may provide a new direction for the treatment of pterygium.

Knowledge Graphs (KGs) have shown great success in recommendation. This is attributed to the rich attribute information contained in KG to improve item and user representations as side information. However, existing knowledge-aware methods leverage attribute information at a coarse-grained level both in item and user side. In this paper, we proposed a novel attentive knowledge graph attribute network(AKGAN) to learn item attributes and user interests via attribute information in KG. Technically, AKGAN adopts a heterogeneous graph neural network framework, which has a different design between the first layer and the latter layer. With one attribute placed in the corresponding range of element-wise positions, AKGAN employs a novel interest-aware attention network, which releases the limitation that the sum of attention weight is 1, to model the complexity and personality of user interests towards attributes. Experimental results on three benchmark datasets show the effectiveness and explainability of AKGAN., 11 pages, 4 figures

Electrochemical N2 reduction reaction (NRR) has been considered as a promising and green process to replace conventional Haber−Bosch process. However, the presence of sluggish reaction kinetics and competitive hydrogen evolution reaction (HER) can result in poor activity and unsatisfactory selectivity. Here, we proposed C/MoS2 catalysts by a facile ‘one-pot’ hydrothermal method. Benefiting from porous nanosphere structure, it shows outstanding charge transfer rate, which accelerates NRR kinetics. As a result, C/MoS2 exhibited a conspicuously improved NRR performance with a high Faradaic efficiency (FE) of 8.2% at −0.7 V. In addition, this electrocatalyst showed marvelous stability.

To celebrate the 15th anniversary of China’s WTO accession, this article reveals – through the lens of the author’s experience in government – a continuous thread of the rule of law, from WTO compliance assessments, dispute settlement, and research and education, thereby illustrating the significant impact that the WTO has had on China. To project the future direction and impact, this article concludes by introducing ongoing WTO training in China.

This paper studies the structure of the shielding device of DC device in the UHV converter station. Through simulation analysis, the electric field distribution on the surface of the shielding device is calculated to find the factors that affect the maximum field strength and the maximum electric field of the shielding device at different opening sizes and flange radius. By optimizing the structure and using a lantern-shaped shielding device, the maximum electric field strength on the surface of the shielding device of the same size can be reduced by more than 15%. The research of this project is of guiding significance for the design of shielding devices of UHV DC engineering in high altitude areas, and of great significance for promoting the progress and development of UHV DC transmission technology.

From my eighteen years of work at China's Ministry of Commerce, of which over a dozen years on China WTO cases, from the first-ever U.S.-Steel Safeguards to most of the important cases, I try to provide in this article a general understanding in China: WTO dispute settlement system is a peaceful and an effective way to solve trade issues between China and other WTO members, and China is becoming more and more confident in this system as it is experiencing more and more cases. The 'evidence' is found in training courses and seminars on the WTO in the early days, its first 'exciting' case, the first five 'quiet' years, the second five 'noisy' years, and the subsequent 'normal' years. It concludes by introducing the group of people working in this area, pointing out the significance of these cases, i.e., the rule of law in China, and expecting a better future for both China and the WTO with academic research and school teaching.

Trace element levels are associated with the incidence of osteoporotic fractures, but related mechanisms remain unknown. Trace elements may interfere with growth, development and maintenance of bones. Therefore, we investigated whether plasma trace element levels are associated with bone mineral density in elderly males in Beijing. After epidemiologically investigating 91 elderly males with age ranging from 50 years to 80 years, we obtained a total of 30 healthy (group 1), 31 osteopoenic (group 2) and 30 osteoporotic (group 3) subjects. Blood was collected, and serum concentrations of trace elements were detected. Elderly males in the three groups were carefully matched in terms of body mass index. Iron, manganese, zinc, copper, selenium, cadmium and lead were analysed by inductively coupled plasma-mass spectrometry. Bone mineral density (BMD) was measured by QDR-2000 dual-energy X-ray absorptiometry. Correlation between BMD and serum element contents was analysed using SPSS16.0. The plasma levels of manganese, zinc, copper, selenium and lead were similar in all of the groups (P>0.05). Cadmium was significantly and negatively correlated with BMD of the lumbar vertebrae (P

Some crustal-deformation data related to the Ms8.0 Wenchuan in 2008, was described and a model that is capable of explaining the observed deformation features is presented. The data include: pre-earthquake uplift in an area south of the epicenter obtained by repeated-leveling measurements; pre-earthquake horizontal deformation by GPS observation during two periods in Sichuan-Yunnan area; vertical deformation along a short cross-fault leveling line in the epicenter area; and co-seismic near-field vertical and horizontal crustal-movement data by GPS. The model is basically “elastic-rebound”, but involves a zone between two local faults that was squeezed out at the time of earthquake.

There exists many kinds of calculation models of plane and spherical strain fields, but the results of these models are different. The representative models was analyzed, and got some useful conclusions, in which some models are unbiased, some have deviations that can be corrected, some can only be used to compute strain in a uniform medium and can not be extended, and some can be used in the calculation and analysis of continuous strain field as well. Meanwhile, the correction relationship for spherical difference movement (displacement) computed from strain results was given, and the meaning of the non – differential term in spherical strain model was demonstrated.

A novel cluster beam deposition method of energetic cluster impact (ECI) is applied in the preparation of metallic films and compound films. A quartz crystal oscillator is used to measure the deposit rate of the films. It is found that it can reach up to 10 nm/min. The influence of deposition parameters on the properties of the films has been investigated preliminarily using atomic force microscopy (AFM) and Rutherford Backscattering Spectroscopy (RBS). The AFM results show that the morphology of the films is very sensitive to the sputter current and the cluster energy. The RBS spectra reveal that the impurity level in the films is very low and the film thickness is varied with the cluster impact energy, the pressure in the sputter chamber, etc. The experimental results indicate that smooth, compact and uniform films with strong adhesion have been successfully prepared.

To investigate the differences in the amount of cancer stem cells in different breast cancer subtypes.THE SPECIMENS OF BREAST CANCER TISSUES WERE DIVIDED INTO FIVE GROUPS: group A (luminal A type), B (luminal B type), C (HER-2 + type), D (basal-like type) and E (normal-like type) according to their molecular subtypes. The cancer stem cell spheres in each group were measured through colony formation method, and then the relations of the amount of cancer stem cells with the subtypes of breast cancer were analyzed.The numbers of cancer stem cell spheres in group A and B were (1.1±0.2)/1,000 cells and (1.3±0.1)/1,000 cells, respectively, and this had no significant difference (P0.05). The number of cancer stem cell spheres in group C was (8.6±1.0)/1,000 cells, which was significantly higher than that in group A and B (both P0.05). The numbers of cancer stem cell spheres in group D and E were (22.4±1.2)/1,000 cells and (17.7±2.0)/1,000 cells, respectively, and this was statistically similar (P0.05) but either was significantly higher than that in the other three groups (all P0.05).Breast cancer tissues of different molecular subtypes contain varying amounts of cancer stem cells, and this may have certain significance for predicting the prognosis of breast cancer.

In order to solve the engineering construction problem of lightning protection in permafrost regions along the Qinghai-Tibet railway, based on the soil characteristics in plateau permafrost regions, Zhongguang Hi-Tech Industrial Development Group set up an earthing test base in Balang mountain, the permafrost condition of which is very similar to that of Qinghai-Tibet railway. Field tests of reducing the earthing resistance were conducted there. This paper introduces the low resistance earthing module and the rationale in its function of reducing earthing resistance. Then the paper briefly describes the test procedure and presents the test result and analysis of test data. The test result verifies that the low resistance earthing module has much better effect than other earthing products in plateau permafrost regions. It also provides some instructive implications for the selection of earthing devices for Golmud-Lhasa section of Qinghai-Tibet railway.

The paper introduces a new lightning protection system of vehicles running at a high speed. The lightning rod for direct lightning protection can reduce lightning interception probability to a level as low as possible so as to minimize damage of vehicles by direct lightning stroke. SPDs are provided for protection of corresponding power supply, signal, and antenna feed ports of equipments and systems installed inside vehicles. Equipotential bonding is adopted to prevent back flashover due to different earth potentials. The vehicles as well as their electronic equipments and systems inside can thus be effectively protected against lightning and their safety can be ensured. Finally, the paper introduces a quick-installation earthing electrode used specially for military vehicles requiring low earthing resistance when they stop at a military position.

Abscisic acid (ABA) is an important plant hormone for a wide array of growth and developmental processes and stress responses, but the mechanism of ABA signal perception on the plasma membrane remains to be dissected. A previous GeneChip analysis revealed that a member of the A4 subfamily of lectin receptor kinases (LecRKs) of Arabidopsis (Arabidopsis thaliana), At5g01540 (designated LecRKA4.1), is up-regulated in response to a low dose of ABA in the rop10-1 background. Here, we present functional evidence to support its role in ABA response. LecRKA4.1 is expressed in seeds and leaves but not in roots, and the protein is localized to the plasma membrane. A T-DNA knockout mutant, lecrka4.1-1, slightly enhanced ABA inhibition of seed germination. Interestingly, LecRKA4.1 is adjacent to two other members of the A4 subfamily of LecRK genes, At5g01550 (LecRKA4.2) and At5g01560 (LecRKA4.3). We found that loss-of-function mutants of LecRKA4.2 and LecRKA4.3 exhibited similarly weak enhancement of ABA response in seed germination inhibition. Furthermore, LecRKA4.2 suppression by RNA interference in lecrka4.1-1 showed stronger ABA inhibition of seed germination than lecrka4.1-1, while the response to gibberellic acid was not affected in lecrka4.1-1 and lecrka4.1-1; LecRKA4.2 (RNAi) lines. Expression studies, together with network-based analysis, suggest that LecRKA4.1 and LecRKA4.2 regulate some of the ABA-responsive genes. Taken together, our results demonstrate that the A4 subfamily of LecRKs has a redundant function in the negative regulation of ABA response in seed germination.

The question of whether ion beam analysis technique can be applied to the study of polymers has been investigated. Degradation of mylar foil under MeV ion beam irradiation was observed. In order to describe the degradation process of mylar foil under ion beam irradiation quantitatively, only one dose-independent degradation cross section for each of hydrogen and oxygen was needed. Our results suggest that proton or He+ ion combined with rotation of the target (scanning area of 20 mm2) can be used to study the mylar foil without substantially changing the compositions of the target up to ion fluence 5 × 1015/cm2.

The proton elastic scattering (PES) technique in the energy range of 2.5–3.6 MeV for light elements C, N and O detection has been investigated by measuring the enhanced scattering cross sections at 170°. It is found that at the incident proton energy near 3.0 MeV the scattering cross sections for all three light elements vary rather smoothly. The results show that PES technique with proton energy near 3.0 MeV may be used for simultaneously profiling carbon, nitrogen and oxygen over a reasonable depth in a heavy matrix.

The problem of labor employment is a major problem of global dimensions. It is an especially pronounced problem in a country such as ours, with our tremendous population and our relatively poor background. However, under the leadership of the Central Committee and the State Council, and with the coordinated effort of all the localities, departments, and circles in society, we have achieved in the area of labor employment a tremendous success that has captured the attention of the entire world.

Crustal movement and incremental-movement data observed repeatedly at GPS stations during 1999–2009 were analyzed to study the effect of two earthquakes of Ms8.1 and Ms8.0 that occurred in 2001 and 2008, respectively, in Qinghai-Tibet sub-plate and its eastern margin. The result revealed certain anomalous pre-earthquake deformation and some large co-seismic changes. Prior to the 2008 Wenchuan Ms8.0 earthquake, the seismogenic Kunlunshan fault zone became a geographic boundary between different regional movements. At the time of the earthquake, there was an average cross-fault crustal shortening of − 1.04 m and an average right-lateral strike slip of 0.76 m along the ruptured segment, as well as a strain-energy release of − 62. 66 × 10.7.